Mason Eye Institute, University of Missouri School of Medicine, Columbia, MO, USA.
Mol Genet Metab. 2010 Aug;100(4):349-56. doi: 10.1016/j.ymgme.2010.04.009. Epub 2010 Apr 24.
The neuronal ceroid lipofuscinoses (NCLs) are lysosomal storage diseases characterized by progressive neurodegeneration and accumulation of autofluorescent storage granules. A 9-month-old Miniature Dachshund presented with NCL-like signs that included disorientation, ataxia, weakness, visual impairment, and behavioral changes. Neurons throughout the CNS contained autofluorescent lysosomal inclusions with granular osmiophilic deposit (GROD) ultrastructure characteristic of classical infantile NCL (INCL). Human INCL is an autosomal recessive disorder that results from mutations in PPT1, a gene that encodes the enzyme palmitoyl protein thioesterase 1 (PPT1; EC 3.1.22). Resequencing of PPT1 from the affected dog revealed that the dog was homozygous for a single nucleotide insertion in exon 8 (PPT1 c.736_737insC), upstream from the His289 active site. Brain tissue from this dog lacked PPT1 activity. The sire and dam of the propositus were heterozygous for the c.736_737insC mutation; whereas, 127 unrelated Dachshunds were homozygous for the wild-type allele. This is the first reported instance of canine NCL caused by a mutation in PPT1.
神经元蜡样质脂褐质沉积症（NCLs）是一种溶酶体贮积病，其特征是进行性神经退行性变和自发荧光贮积颗粒的积累。一只 9 个月大的迷你腊肠犬出现了类似 NCL 的症状，包括定向障碍、共济失调、虚弱、视力障碍和行为改变。中枢神经系统中的神经元含有自发荧光溶酶体内含物，具有颗粒性亲脂性沉积物（GROD）超微结构，这是典型婴儿型 NCL（INCL）的特征。人类 INCL 是一种常染色体隐性疾病，是由编码棕榈酰蛋白硫酯酶 1（PPT1；EC 3.1.22）的酶 PPT1 基因中的突变引起的。受影响的狗的 PPT1 重测序显示，狗在 His289 活性位点上游的外显子 8（PPT1 c.736_737insC）中纯合了单个核苷酸插入。这条狗的脑组织缺乏 PPT1 活性。先证犬的父亲和母亲均为 c.736_737insC 突变的杂合子；而 127 只无关的腊肠犬则为野生型等位基因的纯合子。这是首例由 PPT1 突变引起的犬 NCL 报告。
